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Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2
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Zeitschriftentitel: | Journal of Virology |
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Personen und Körperschaften: | , , , , , , |
In: | Journal of Virology, 87, 2013, 20, S. 11160-11167 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
American Society for Microbiology
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Schlagwörter: |
Zusammenfassung: | <jats:title>ABSTRACT</jats:title> <jats:p> Nonstructural protein 4 (NSP4), encoded by rotavirus, exhibits various properties linked to viral pathogenesis, including enterotoxic activity. A recent study (O. V. Kavanagh et al., Vaccine 28:3106-3111, 2010) indicated that NSP4 also has adjuvant properties, suggesting a possible role in the innate immune response to rotavirus infection. We report here that NSP4 purified from the medium of rotavirus-infected Caco-2 cells triggers the secretion of proinflammatory cytokines from macrophage-like THP-1 cells and nitric oxide from murine RAW 264.7 cells. Secretion is accompanied by the stimulation of p38 and JNK mitogen-activated protein kinases (MAPKs) and nuclear factor NF-κB. NSP4 triggered the secretion of cytokines from murine macrophages derived from wild-type but not MyD88 <jats:sup>−/−</jats:sup> or Toll-like receptor 2 (TLR2 <jats:sup>−/−</jats:sup> ) mice and induced secretion of interleukin-8 (IL-8) from human embryonic kidney cells transfected with TLR2 but not TLR4. Our studies identify NSP4 as a pathogen-associated molecular pattern (PAMP) encoded by rotavirus and provide a mechanism for the production of proinflammatory cytokines associated with the clinical symptoms of infection in humans and animals. </jats:p> |
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Umfang: | 11160-11167 |
ISSN: |
0022-538X
1098-5514 |
DOI: | 10.1128/jvi.03099-12 |